1. Field of the Invention
The present invention relates to a process for nitrosating compounds containing an active hydrogen bonded to a carbon atom.
2. Description of the Background
Nitrosation products of C-H-acidic compounds are used as intermediates in the preparation of the corresponding amines, which are, in turn, useful in synthesizing a variety of pharmaceuticals and active agents for plant protection products. Hydroxyimino and nitroso compounds of malonic acid derivatives are examples of these nitrosation products. Many processes for nitrosation of malonic acid derivatives, such as esters, amides, imidoesters and malononitrile, are known. For example, J. B. Paine III et al., in J Org. Chem., 50 (1985), 5598-5604, describe a process for preparing diethyl hydroxyiminomalonate by slowly adding an aqueous solution of sodium nitrite to a solution of diethyl malonate in glacial acetic acid, adding sodium hydroxide solution to the homogeneous reaction mixture, followed by separating the reaction product from the aqueous phase by extraction with diethyl ether. This process produces an aqueous solution containing sodium acetate in approximately 4 times the molar amount of the diethyl malonate.
In German Offenlegungsschrift 23 52 706, ethyl cyanoacetate is first converted to diethyl monoimidomalonate hydrochloride with hydrogen chloride in absolute alcohol, and then the hydrochloride is dissolved in acetic acid. To this solution is added, gradually, an aqueous solution of sodium nitrite, and, at the end of the nitrosation reaction, water is added to the reaction mixture. The reaction product is separated by solvent extraction of the aqueous phase, which contains the sodium acetate by-product of the formation of nitrous acid.
EP-A1-0 517 041 discloses preparing dimethyl hydroxyiminomalonate by adding sodium nitrite and acetic acid to a mixture of dimethyl malonate and water. The reaction mixture is extracted twice using dichloroethane in order to separate the diethyl hydroxyiminomalonate from the sodium acetate, which remains in the aqueous phase. Although sodium nitrite is used only in amounts of 1.2 mol per mole of malonate, the reaction time of 21 hours makes this reaction virtually unusable as an industrial process. Furthermore, the process is unsuitable for reacting malonates of low water solubility.
All of the processes discussed above produce sodium acetate in the form of impure aqueous solutions, which are difficult to dispose of. These processes are, therefore, ecologically unsuitable on an industrial scale.
DE 954 873 describes a process for the preparation of diethyl hydroxyiminomalonate by dissolving diethyl malonate in a solvent, such as toluene, which is not discernibly miscible with water and can be separated from the end product by distillation. To this solution, at least molar amounts of sodium nitrite and from 1 to 10 percent by weight, based on the malonate, of water are added, followed by gradual addition of acetic acid to the suspension at 30.degree. to 70.degree. C. When the nitrosation is finished, the undissolved sodium acetate is separated from the reaction solution and crystallized diethyl hydroxyiminomalonate is obtained from the filtered solution. This process requires no solvent extraction, and indeed about 2/3 of the sodium acetate is obtained in solid form. The process claims to give "smooth and fast reactions and good yields". The latter, at least, is not correct, because the resulting crystalline product having a melting point of 86.5.degree.-88.degree. C. was not diethyl hydroxyiminomalonate, but instead, a complex with sodium acetate. This nitrosation product is so impure that hydrogenation to diethyl acetaminomalonate on platinum catalysts in acetic anhydride, a preferred solvent, is not possible.
Accordingly, there remains a need for a method of nitrosating C-H-acidic compounds that avoids these disadvantages and provides reaction products that can be converted to the corresponding amines.